Abstract
Objective: The goal of the current study was to investigate the possible use of solid lipid nanosuspension (SLNs) as a drug delivery method to boost doxorubicin (DOX) brain-targeting performance after intranasal (i. n.) administration. 
 Methods: 33 factorial design was applied for optimization by using lipid concentration, surfactant concentration, and High-speed homogenizer (HSH) stirring time as dependent variables, and their effect was observed on particles size, Polydispersity index (PDI), and entrapment efficiency. 
 Results: With the composition of Compritol® 888 ATO (4.6 % w/v), tween 80 (1.9 % w/v), and HSH stirring time, the optimized formula DOX-SLNs prepared (10 min). Particle size, PDI, zeta potential, entrapment efficiency, percent in vitro release were found to be 167.47±6.09 nm, 0.23±0.02, 24.1 mV, 75.3±2.79, and 89.35±3.27 percent in 24 h, respectively, for optimized formulation (V-O). No major changes in particle size, zeta potential, and entrapping efficiency were found in the stability studies at 4±2 °C (refrigerator) and 25±2 °C/60±5% RH up to 3 mo. 
 Conclusion: Following the non-invasive nose-to-brain drug delivery, which is a promising therapeutic strategy, the positive findings confirmed the current optimized DOX-loaded SLNs formulation.
Highlights
The most widely used cancer treatment is through chemotherapy administered either by the intravenous or oral route, which harms the normal cells more than just the cancerous cells in the body and causes many unwanted side effects [1].Doxorubicin hydrochloride (DOX) is a broad spectrum anthracycline anticancer drug administrated intravenously, including the US Food and Drug Administration (USFDA) approved pegylated liposomal doxorubicin marketed as Doxil® for treatment of numerous human cancers [2,3,4]
The applicability of Compritol 888 ATO in the preparation of aqueous colloidal dispersions such as solid lipid microparticles (SLMs), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) to capture lipophilic drugs has been highlighted in various research studies [14,15,16,17,18,19,20]
The results showed that the kinetic models that could be used to characterize the release characteristics of doxorubicin-loaded lipid nanosuspension (DOX-solid lipid nanosuspension (SLNs)) formulations were better suited to the zero-order model
Summary
Doxorubicin hydrochloride (DOX) is a broad spectrum anthracycline anticancer drug administrated intravenously, including the US Food and Drug Administration (USFDA) approved pegylated liposomal doxorubicin marketed as Doxil® for treatment of numerous human cancers [2,3,4]. Intranasal administration is a non-invasive way that can deliver drugs directly into the brain, bypassing BBB through the trigeminal or olfactory pathway. It has been exploited by researchers, followed by the advantages of self-medication, ease delivery, avert first-pass metabolism, rapid onset, reduction in dose amount when compared to oral route [6]
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